Background: Limited data on the prevalence and medical care of sickle cell disease (SCD) in Germany are available. Here, we make use of a patient registry to characterize the burden of disease and the treatment modalities for patients with SCD in Germany.Procedure: A nationwide German registry for patients with SCD documents basic data on diagnosis and patient history retrospectively at the time of registration. A prospective annual documentation provides more details on complications and treatment of SCD. For the current analyses, data of 439 patients were available.Results: Most patients had homozygous SCD (HbSS 75.1%, HbS/β‐thalassemia 13.2%, and HbSC 11.3%). The median age at diagnosis was 1.9 years (interquartile range, 0.6‐4.4 years), most patients were diagnosed when characteristic symptoms occurred. Sepsis and stroke had affected 3.2% and 4.2% of patients, respectively. During the first year of observation, 48.3% of patients were admitted to a hospital and 10.1% required intensive care. Prophylactic penicillin was prescribed to 95.6% of patients with homozygous SCD or HbS/β thalassemia below the age of six and hydroxycarbamide to 90.4% of patients above the age of two years. At least one annual transcranial Doppler ultrasound was documented for 74.8% of patients between 2 and 18 years.Conclusion: With an estimated number of at least 2000, the prevalence of SCD in Germany remains low. Prospectively, we expect that the quality of care for children with SCD will be further improved by an earlier diagnosis after the anticipated introduction of a newborn screening program for SCD.

Sickle cell disease (SCD) is a severe non-malignant disorder of hemoglobin and is inherited in an autosomal-recessive manner

Sickle Cell Disease (SCD) is the most common monogenic disorder globally but qualifies as a rare disease in Germany. In 2012, the German Society for Paediatric Oncology and Haematology (GPOH) mandated a consortium of five university hospitals to develop a disease management program for patients with SCD. Besides other activities, this consortium issued treatment guidelines for SCD that strongly favour the use of hydroxyurea and propagated these guidelines in physician and patient education events. In order to quantify the effect of these recommendations, we made use of claims data that were collected by the research institute (WIdO) of the major German insurance company, the Allgemeine Ortskrankenkasse (AOK), and of publicly accessible data collected by the Federal Statistical Office (Statistisches Bundesamt, Destatis). While the number of patients with SCD in Germany increased from approximately 2200 in 2011 to approximately 3200 in 2019, important components of the recently issued treatment guidelines have been largely implemented. Specifically, the use of hydroxyurea has more than doubled, resulting in a proportion of approximately 44% of all patients with SCD being treated with hydroxyurea in 2019. In strong negative correlation with the use of hydroxyurea, the frequency of acute chest syndromes decreased. Similarly, the proportion of patients who required analgesics and hospitals admissions declined. In sum, these data demonstrate an association between the dissemination of treatment guidelines and changes in clinical practice. The close temporal relationship between the increased use of hydroxyurea and the reduction in the incidence of acute chest syndrome in a representative population-based analysis implies that these changes in clinical practice contributed to an improvement in key measures of disease activity.

HSCT is curative in SCD. Patients with HLA‐identical sibling donor have an excellent outcome ranging from 90%‐100% overall and event‐free survival. However, due to the lack of matched sibling donors this option is out of reach for 70% of patients with SCD. The pool of potential donors needs to be extended. Transplantations from HLA‐matched unrelated donors were reported to be less successful with shorter event‐free survival and higher incidences of complications including graft‐vs‐host disease, especially in patients with advanced stage SCD. Here we report transplantation outcomes for 25 children with SCD transplanted using HLA‐matched grafts from related or unrelated donors. Overall survival was 100% with no severe (grade III‐IV) graft‐vs‐host disease and a 12% rejection rate. Mixed donor chimerisms only occurred in transplantations from siblings, while transplantations from unrelated donors resulted in either complete donor chimerism or rejection. Despite the small patient number, overall and disease‐free survival for unrelated donor transplantations is excellent in this cohort. The advanced disease state, higher alloreactive effect and stronger immunosuppression in unrelated donor transplantations raises patient risk, for which possible solutions could be found in optimization of transplant preparation, graft manipulation or haploidentical transplantation using T cell receptor α/β‐depleted grafts.

Background: New strategies to optimize donor selection for hematopoietic stem cell transplantation (HSCT) have mainly been evaluated in adults, but the disease spectrum requiring HSCT differs significantly in children and has consequences for the risk of complications, such as graft‐versus‐host disease (GvHD).Procedures: Here we evaluated whether HLA‐DPB1 and Predicted Indirectly ReCognizable HLA‐Epitope (PIRCHE) matching can improve donor selection and minimize risks specific for a pediatric cohort undergoing HSCT in Berlin between 2014 and 2016.Results: The percentage of HLA‐DPB1–mismatched HSCT in the pediatric cohort was in line with the general distribution among matched unrelated donor HSCT. Nonpermissive HLA‐DPB1 mismatches were not associated with a higher incidence of GvHD, but the incidence of relapse was higher in patients undergoing HSCT from HLA‐DPB1–matched transplantations. High PIRCHE‐I scores were associated with a significantly higher risk for developing GvHD in patients undergoing HSCT from nine of ten matched unrelated donors. This finding persisted after including HLA‐DPB1 into the PIRCHE analysis.Conclusions: Implementing PIRCHE typing in the donor selection process for HSCT in children could particularly benefit children with nonmalignant diseases and support further validation of PIRCHE‐based donor selection in a larger number of children treated at different sites.

Sickle cell disease (SCD) is considered a rare disease in Germany. Due to the increasing prevalence, the acute and chronic morbidities associated with the disease and the sharp increase in the mortality rate of young adults, a need-based transition structure for patients with SCD in Germany is explicitly required. This is the first multicenter German consensus statement addressing the importance of implementing a standardized transition guideline that allows adolescents and young adults to safely transition from pediatric to adult care. Early identification of medical needs and intervention remains important in the context of chronic diseases. Effective measures can improve health care in general, as they lead to a reduction in disease and the consequential economic burden. It is noteworthy that improving structural barriers remains a key challenge even in highly developed countries such as Germany. Inclusion of these transition services for patients with SCD into the regular care of chronically ill adolescents and young adults should be ensured, as well as the coverage of costs associated with a structured transition process.